During development, the brain is very sensitive to environmental chemicals (toxicants) which can act as teratogens, that is, substances that injure the brain in ways that are more related to when one is exposed than to the specific nature of the compound. One common teratogen is methylmercury (MeHg), to which humans are exposed when consuming normal dietary fish and shellfish. Studies of children from populations that eat a lot of fish suggest that some may have problems with intelligence, language and learning and memory. The effects of a single low-level exposure to MeHg will be studied in the developing rat hippocampus, a brain region where neurogenesis (birth of new neurons) occurs throughout life. It is believed that neurogenesis occurs in the hippocampus because new spatial learning and memory formation may depend on an adequate supply of new neuronal cells. We plan the following aims. First, the developmental period of vulnerability to MeHg exposure and the affected cell populations will be characterized during ages that correspond to the third trimester of human development (postnatal day 7 - P7), prepubescence (P14), and adolescence (P21). Next, the effects of a single early exposure (P7) on later adult neurogenesis (P21, P42) will be studied. Lastly, the cellular events, including calcium levels and mitochondrial function, that lea to MeHg-induced cell death will be determined in a newly developed primary hippocampal neural stem cell culture model. This study will help the scientific community gain insights into th effects of MeHg exposure in a paradigm that might suggest we take greater caution in regulating fish consumption during gestation and development. These same pathways may also be relevant to multiple other teratogenic insults that occur during development, including malnutrition, hypoxia-ischemia, medication and drug abuse and infections.